ACTA ENDOCRINOLOGICA (BUC)

Objective. The aim of the study was to investigate the role of Hepatocyte Growth Factor (HGF)/c-Met pathway in testicular damage provoked by streptozotocin (STZ)- induced diabetes and the effects of insulin treatment on the HGF/c-Met pathway. Methods. Total 21 paraffin-embedded testicular tissues of control (n=7), streptozotocin (STZ)-induced diabetic (n=7) and insulin-treated diabetic (n=7) Wistar albino rats were used in this study. Testicular damage was examined histologically and by Johnsen’s score was also evaluated. Immunohistochemical stainings of HGF and c-Met were analysed by using antibodies against HGF and c-Met. Results. We found the degeneration in seminiferous tubule epithelium and disorganization of spermatogenetic cell series in testis tissues of diabetic rats. We also determined decrease both in seminiferous tubule diameter and Johnsen’s scores in diabetic group. The expressions of HGF and c-Met in seminiferous tubule epithelium and in spermatogenic cells (especially spermatocytes and spermatids) were significantly increased in diabetic rats compared to those of control. Insulin treatment significantly reduced the diabetes-induced morphological changes and HGF/c-Met over expressions in the diabetic rat testis. Conclusion. HGF/c-Met pathway might have a role in diabetes- induced testicular damage. Drugs acting on this pathway might be effective to prevent or delay the testicular damage induced by diabetes.

Background. Gangliosides are Nacetyl - neuraminic - acid containing glycosphyngolipids that modulate several\r\ncellular functions.\r\nObjective. The present study confirmed the presence of cellular gangliosides in melanocytic tumors with\r\nneuroectodermal origin. These molecules showed large quantitative and structural variability in melanocytic cells.\r\nMethods. The spectrum and levels of gangliosides were performed from 1991 until 2010, in 411 specimens of melanoma, 108 cutaneous metastases of melanoma, 206\r\nnevocellular and dysplastic nevus and 130 specimens of normal skin.\r\nResults. Melanoma showed aberrant gangliosides expression. This included overexpression of normal ganglioside\r\nconstituents (GM2, GM3, GD2, GD3), which also appear in melanocytic nevus and epidermis tissues, and expression of\r\ngangliosides (O-Acetyl-Ganglioside) not found in normal adult tissue. The ganglioside composition of\r\nmelanoma is: GM1 (1,29?0,87%), GM2 (10,32?4,11%), GM3 (22,23?11,30%), GD2 (16,03?9,13%), GD3 (39,06?14,25%), GD1a\r\n(2,16?0,77%), GD1b (1,74?1,01%), GT1b (1,82?1,11 %), GQ1b (1,34?1,07%), OAcetyl-GD3 (4,01?2,81%).\r\nConclusions. The overexpression and variability of gangliosides in melanoma and the low expression of them in normal tissue was correlated with oncogenic process and\r\nmetastatic potential.

Hypothalamic kisspeptin signaling has been recently observed to correlate with seasonal breeding in free ranging male rhesus monkeys. Recent evidence also suggests that excitatory and inhibitory amino acid neurotransmitters contribute in regulation of kisspeptin neurons. Objective. The present study was focused on analyzing the interplay of Kiss1 neurons with afferent excitatory and inhibitory signals in the brain of male rhesus monkeys during the breeding and non breeding seasons. We hypothesized that: kisspeptin stimulation may occur due to the increase in N-methyl-D,L-aspartate (NMDA) dependant excitatory inputs and decrease in inhibitory γ-aminobutyric acid (GABA) based cues during the breeding season Materials and Methods. Messenger ribonucleic acid (mRNA) was extracted from the medio basal hypothalamus (MBH) of five free ranging adult male rhesus monkeys (Macaca mulatta) during the breeding season (n=3; October; plasma testosterone levels: 26.15±2.64 nmol/L; testicular volume: 69.00 ± 0.57 ml); and the non-breeding season (n=2; July; plasma testosterone levels: 4.09±1.64 nmol/L; testicular volume: 12.88±0.31 ml). Real time polymerase chain reaction (RT-PCR) was used to quantify the levels of Kiss1, Kiss1r, NR1 and glutamic acid decarboxylase (GAD67) mRNA, relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results. Significantly high (p<0.05) expression of Kiss1, Kiss1r and NR1 mRNA and low (p<0.05) expression of GAD67 mRNA in the hypothalamus were found to be in synchrony with the breeding season. Conclusion. Based on correlative gene expression changes in the adult male monkey hypothalamus we suggest that in higher primates increased kisspeptin signaling during breeding season may be entrained by an increase in NMDA excitatory inputs; while decreased kisspeptin signaling during the non-breeding season may be driven by an increase in GABA based inhibitory cues.

Introduction. Diabetic chronic kidney disease has more fatal clinical progresses and this situation can be related to volume overload, which is seen more commonly in diabetic chronic kidney disease patients than in non-diabetic chronic kidney disease patients. Therefore, we examined the effect of diabetes mellitus on volume overload in newly diagnosed stage 5 chronic kidney disease patients whose volume overloads were not showing signs of improvement from renal replacement therapy. Method. One hundred and five patients (46 diabetic, 59 non-diabetic) with end-stage chronic kidney disease, who had glomerular filtration rate (GFR) under 15 mL/min for at least three months were enrolled in this prospective study. We determined the body volume overload and configuration using a bioimpedance device. NT-proBNP levels were recorded. Results. There was a statistically significant difference between diabetic and non-diabetic groups according to overhydration (OH, p=0.003), extracellular water (ECW, p=0.045), intracellular water (ICW, p<0.001) and OH/ECW (p=0.003). In addition, there was a statistically significant difference between groups in terms of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP levels, p=0.008). Discussion. We compared diabetic and nondiabetic end-stage chronic kidney disease patients who were not in renal replacement therapy yet. We found more volume overload and extracellular fluid volume in the diabetic group.

The determination of cardiac peptides at rest and during exercise stress testing (ET) represents a useful tool for the diagnosis of heart failure patients, but their usefulness in isolated LV diastolic dysfunction was less studied until now.\r\nAim. The aim of this study is to compare the effect of ET upon cardiac peptides in patients with left ventricular systolic and diastolic dysfunction.\r\nMethods. There were studied 101 heart failure patients, 58 with systolic LV dysfunction (LVEF 37.8%) and 43 patients with isolated LV diastolic dysfunction, mainly with hypertension (31 cases). All patients were submitted to a symptom-limited ET on cycloergometer, blood samples being obtained before ET and at peak effort. The plasmatic levels of N terminal pro brain-type natriuretic peptide (NT-proBNP) were determined using ELISA method (n.v. <250 fmol/ml). The systolic and diastolic LV functions were determined by echo-Doppler, according to ESC guidelines.\r\nResults. The results showed that the rest NT-proBNP values were increased in patients with LV systolic dysfunction (640?220 fmol/ml) in comparison with diastolic dysfunction (419 ?120 fmol/ml), p<0.01. At peak effort NT-proBNP increased to 790?242 fmol/ml (23%) in patients with systolic dysfunction (p<0.04) and to 490.2?179 fmol/ml (17%) in patients with diastolic dysfunction (p= NS). There was a close relationship between rest and exercise NT-proBNP values in both systolic (r=0.99, p< 0.05) and diastolic (r=0.72) LV dysfunction. \r\nIn conclusion, in heart failure patients with both systolic and diastolic LV dysfunction, NT-proBNP is increased at rest and during exercise, the increase being significant for patients with LV systolic dysfunction, probably in relationship with more important hemodynamic abnormalities.

A study was performed on the basis of multiple-choice questionnaires applied to a lot of 96 pupils in the forms 9 to 11 at a high-school in the city of Suceava. The questionnaires of 96 de respondents were analysed ? 42 teenage boys (13 from the rural environment, 29 from the urban environment) and 54 teenage girls (19 from the rural environment and 35 from the urban environment). The objectives of the questions were: clarifying the relationships between the teenager and the social and family environment, affiliation to the reference group, knowledge and attitudes concerning the various aspects of sex life: the affective component, the start of sexual activity, notions about contraception and STD-s, the teenagers? attitude concerning the introduction of sex education in school. Most of the teenagers have an optimistic projection on the society?s permissive mentality concerning them and they enjoy a favourable family climate. Affiliation to the peer group, as a reference group, is based on fundamentally positive criteria and moral values and less based on professional interests. Love is perceived in an ideal manner, especially by teenage girls. The optimal age for becoming sexually active is declared as being 16-18 by most of the boys and 19-21 by most of the girls. The notions about contraception have a general character, and their practical application is more frequent with the boys than with the girls. The notions about sexually transmitted diseases, risk and prevention, are slightly better in boys than in girls. The main sources of information the teenagers have about their own sexuality are the media, more than the family and the educators. Although most of the teenagers agree with the need to have sex education in school, they could not offer solutions on the practical ways of delivering this education.

Objective. The existing studies involving omentin-1 have mainly focused on relationships with single cardiovascular risk factor. Whether omentin-1 is associated with the aggregation of cardiovascular risk factors has not been reported. We investigate the relationship between the serum omentin-1 level and aggregation of cardiovascular risk factors in adolescents. Subjects and Methods. A total of 741 young students, 11–16 years of age, were enrolled using a stratified cluster sampling method. The participants were given a questionnaire survey and underwent a physical examination. The aggregation of cardiovascular risk factors was defined as two or more cardiovascular risk factors occurring simultaneously in the same individual. Results. Partial correlation analysis suggested that serum omentin-1 level was significantly correlated with waist circumference (R=-0.086, P=0.019) and Body Mass Index (R=-0.096, P=0.009). Logistic regression analysis showed that as the serum omentin-1 level increased, the risk of aggregation of cardiovascular risk factors decreased. Cardiovascular risk factors which were most closely associated with a decrease in the serum omentin-1 level were obesity calculated by Body Mass Index (OR=0.988, P=0.043) and central obesity calculated by waist circumference (OR=0.993, P=0.012). Conclusions. The serum omentin-1 level in adolescents is inversely associated with the aggregation of cardiovascular risk factors. Waist circumference and Body Mass Index are factors most closely associated with a decrease in the serum omentin-1 level.

Introduction. Primary hyperparathyroidism is diagnosed earlier and more frequently with the introduction of routine serum calcium measurements. In literature, it is shown that mortality and morbidity decrease after parathyroidectomy. In our study, we aimed to determine the effect of parathyroidectomy on oxidative stress. Materials and Methods. The results of 41 patients who underwent parathyroidectomy for primary hyperparathyroidism between March 2018 and end of December 2018 were evaluated prospectively. Total antioxidant capacity (TAC), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), 8-hydroxy- 2’-deoxyguanosine (8-OHdG), malondialdehyde (MDA), parathyroid hormone, calcium and albumin were measured before and after parathyroidectomy. Results. The mean age of the patients in the study was 45 ± 13.1 years (age range: 18-76 years). The female/ male ratio was 32/9. Postoperative values of 8OHdG, MDA and SOD 1 were significantly lower than preoperative values (p <0.05). There was no significant difference between preoperative and postoperative TAC and TBARS values. Conclusion. Oxidative stress decreased in patients with primary hyperparathyroidism after parathyroidectomy. Randomized prospective studies are needed to show the relationship between biochemical and clinical parameters in order to see the clinical reflection of the study.

Context. Diverse physiological or pathological events which are stimulated or contributed by HGF/c-Met pathway overlap by processes that play roles in etiopathogenesis of diabetes. Objective. In this study, it was aimed to analyse hepatocyte growth factor (HGF) and its receptor c-Met by immunohistochemistry in the heart and aorta tissues of diabetic and insulin-treated diabetic rats. Subjects and Methods. Accordingly, 21 rats were (equally) divided into three groups: Control (C), Diabetic (D), and Insulin-treated Diabetic (D + I). Rats were treated with Streptozotocin (STZ) (45 mg/kg, i.p.) to induce diabetes. Rats in the control group were given saline once a day for 8 weeks, while rats in the D + I group received 6 U/kg NPH insulin once daily for 8 weeks. The heart and aorta tissues were examined with immunohistochemistry, using antibodies against HGF and c-Met. Results. HGF and c-Met expressions were observed to be increased both in heart and aorta tissues in group D, whereas they decreased in group D+I. Conclusions. As a result, insulin treatment was determined to have a reducing effect on the increased expression of HGF and c-Met in diabetic heart and aorta. According to our results, increased HGF ve c-Met values observed in the myocardium and aorta in diabetes, are shown to increase in parallel to tissue damage and decrease by insulin treatment which is an effective therapy method.

Context. Aromatase is a key enzyme in local estrogen production by androgen conversion, especially in women post-menopause. There have been controversies concerning aromatase localization in breast carcinomas and its association with current histopathological variables. Material and Methods. Using polyclonal antibody immunohistochemistry we assessed (by intensity and percentage scores) the immunolocalization of aromatase in 70 tissue samples, and described particularities within the molecular subtypes of breast cancer. Results. Aromatase was found in all tissue compartments: tumor (95.7%), stroma (58.6%) and adipose tissue (94.3%). Aromatase expression in tumor cells correlated inversely with tumor grading (p=-0.361, p=0.027), and positively with estrogen receptor status (ER, p=0.143, p<0.001). Dividing the study group by intrinsic subtypes, a strongly inversely association between tumor aromatase and grading (p=-0.486, p<0.001), and between stromal aromatase and Ki67-index (p=-0.448, p=0.048) was observed in luminal A breast cancer. Tumor aromatase and ER percentage scores had stronger correlations in luminal B HER2 negative (p=0.632, p=0.002), and positive (p=0.324, p=0.026) tumors. In contrast, in triple negative tumors, a positive association stromal aromatase and Ki67 index (p=- 0.359, p=0.007) was observed. Conclusion. Local aromatase was linked to better tumor differentiation and proliferation in luminal breast subtypes, and not in triple negative cases, suggesting a potential prognostic role of aromatase in breast carcinomas.